Protective effect of Dl-3n-butylphthalide on learning and memory impairment induced by chronic intermittent hypoxia-hypercapnia exposure.
Protective effect of Dl-3n-butylphthalide on learning and memory impairment induced by chronic intermittent hypoxia-hypercapnia exposure.
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DOI：
10.1038/srep05555
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发表时间：
2014-07-03
影响因子：
4.6
通讯作者：
Wang XT
中科院分区：
文献类型：
--
作者：
Min JJ;Huo XL;Xiang LY;Qin YQ;Chai KQ;Wu B;Jin L;Wang XT
认知障碍是慢性阻塞性肺疾病（COPD）患者的常见发现，但很少有人关注这种并发症的治疗干预。慢性间歇性低氧高碳酸血症（CIHH）暴露被认为是COPD发病机制的重要组成部分。DL-3正丁基苯酞（NBP）是从芹菜中提取的一种具有广谱神经保护作用的化合物。我们的研究旨在探讨NBP对CIHH诱导的认知障碍的潜力。采用Morris水迷宫评价CIHH暴露后大鼠的认知功能，结果显示NBP治疗组在航行试验中表现更好。NBP激活BDNF和磷酸化CREB，两者都负责神经保护。此外，NBP减少CIHH诱导的细胞凋亡。此外，NBP还诱导了HIF-1α的表达，并上调了自噬蛋白Bnip 3、Beclin-1和LC 3-II的表达。NBP还逆转了SIRT 1和PGC-1α的表达下降，但Tfam、考克斯II和mtDNA的表达保持不变。这些结果表明，NBP在CIHH条件下的神经保护作用可能是通过抑制细胞凋亡、促进缺氧诱导的自噬和激活SIRT 1/PGC-1α信号通路来实现的，而刺激线粒体生物合成可能不是其特征性反应。
Cognitive impairment is a common finding in patients with chronic obstructive pulmonary disease (COPD), but little attention has been focused on therapeutic intervention for this complication. Chronic intermittent hypoxia hypercapnia (CIHH) exposure is considered to be responsible for the pathogenesis of COPD. Dl-3n-Butylphthalide (NBP), extracted from Apium graveolens Linn, has displayed a broad spectrum of neuroprotective properties. Our study aimed to investigate the potential of NBP on CIHH-induced cognitive deficits. The cognitive function of rats after CIHH exposure was evaluated by the Morris water maze, which showed that the NBP treated group performed better in the navigation test. NBP activated BDNF and phosphorylated CREB, the both are responsible for neuroprotection. Additionally, NBP decreased CIHH induced apoptosis. Moreover, NBP further induced the expression of HIF-1α, accompanied by the up-regulation of the autophagy proteins Bnip3, Beclin-1 and LC3-II. Finally, NBP also reversed the decreased expression of SIRT1 and PGC-1α, but the expression of Tfam, Cox II and mtDNA remained unchanged. These results suggested that the neuroprotective effects of NBP under CIHH condition possibly occurred through the inhibition of apoptosis, promotion of hypoxia-induced autophagy, and activation of the SIRT1/PGC-1α signalling pathway, while stimulation of mitochondrial biogenesis may not be a characteristic response.
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